Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines

Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resist...

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Main Authors: Jiandong Li, Yanxin Hu, Jiayao Zhang, Weiguang Zhang, Jianhua Yu, Baochun Lu
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-89423-0
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author Jiandong Li
Yanxin Hu
Jiayao Zhang
Weiguang Zhang
Jianhua Yu
Baochun Lu
author_facet Jiandong Li
Yanxin Hu
Jiayao Zhang
Weiguang Zhang
Jianhua Yu
Baochun Lu
author_sort Jiandong Li
collection DOAJ
description Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.
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spelling doaj-art-0cbd0f244f0743139c99e903f5f2ec8d2025-02-09T12:37:41ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-025-89423-0Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell linesJiandong Li0Yanxin Hu1Jiayao Zhang2Weiguang Zhang3Jianhua Yu4Baochun Lu5Department of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalShaoxing University Affiliated First HospitalZhejiang University School of MedicineDepartment of Molecular Medicine and Clinical Laboratory, Shaoxing Second HospitalDepartment of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalDepartment of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalAbstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.https://doi.org/10.1038/s41598-025-89423-0
spellingShingle Jiandong Li
Yanxin Hu
Jiayao Zhang
Weiguang Zhang
Jianhua Yu
Baochun Lu
Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
Scientific Reports
title Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
title_full Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
title_fullStr Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
title_full_unstemmed Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
title_short Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
title_sort establishment and characterization of three gemcitabine resistant human intrahepatic cholangiocarcinoma cell lines
url https://doi.org/10.1038/s41598-025-89423-0
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